The Animal Core Unit will be responsible for the procurement, maintenance, surgical manipulation, and treatment of viral antibody free (VAF) experimental animals in the Program Project. These are services not provided by Department of Animal Medicine through its per diem charge which includes only food, water, bedding, and cage cleaning. All Program Project experiments will utilize VAF animals housed in a limited access facility designed to maintain the highest degree of cleanliness. The emphasis on VAF animals will preclude contamination of outcomes by infectious agents. Viral infection in particular not only affects the survival of transplant recipients but also modulates many of the processes to be studied in this Program. The objectives and responsibilities of the Program Project Animal Core Unit are as follows: 1. Procurement, quarantine, and housing arrangements and overall responsibility for the maintenance and verification of viral antibody free status of animals used in this Project. 2. Selective breeding oftransgenic and knockout mice, and congenic strains as directed by project directors. 3. Generation of new mouse strains. 4. Genotype verification of all transgenic and knockout mouse strains. 5. Generation of required "synchimeric" gratt recipients. 6. Experimental manipulation of animals while maintaining VAF status as required by Program Project investigators, including allogeneic skin transplantation. Administration of reagents, including anti-CD154 mAb, other monoclonal antibodies, and other specific agents to be developed in the course of the Program; administration of cells in adoptive transfer studies; preparation of specimens (e.g. peripheral blood, nephrectomy specimens containing islet grafts) obtained under conditions that permit continued VAF status. 7. Testing experimental animals for diabetes and skin gratt rejection. In brief, the Animal Core will provide essential assistance to each Program Project with the management and execution of in vivo studies conducted under viral antibody free conditions. It will maintain all records of animals and procedures and serve as a central facility for the cooperative efforts of the program projects.